ABSTRACT The primary objective of this study is to identify, describe, and differentiate stable and persistent patterns in trajectories of ENDS use, from 11 to 22 years of age. Seventy percent of adolescent never users will be susceptible to ENDS and other tobacco use by the age of 17 ? and, by age 22, in young adulthood, the same proportion will have ever used ENDS or tobacco. Understanding what accelerates this rapid progression in tobacco use behaviors and related outcomes from them (e.g., nicotine dependence) will help inform the development of effective interventions. Considerable controversy exists regarding the role that electronic nicotine delivery systems (ENDS) play in the uptake, progression, and/or cessation of combustible tobacco product use, and appropriate ways to measure and model this. To date, almost all studies of ENDS use behaviors are either cross-sectional or limited to short-term (e.g., 1 year) follow-up, which is inadequate for identifying sustained patterns in ENDS use trajectories across the life course, given that transitions in tobacco use behaviors (i.e., initiation to sustained use or quitting) and between tobacco products (e.g., ENDS and cigarettes) are frequent and erratic. Longer-term studies of patterns in ENDS use trajectories are critical, but they will require additional data collection efforts; especially, regionally. Using a cohort-sequential design, we propose to follow and connect 3 existing, population-based cohorts of adolescents (11-15 years old at Wave 1, 2014-15) through young adulthood (18-22 years old at Wave 14, 2021), to represent developmental changes in ENDS use behaviors across these critical stages in the life course. At Wave 1, during the 2014-15 academic year, the sample included 3,907 (N=461,069) students in the 6th, 8th, and 10th grades in 79 middle schools and high schools (N=1969) in the 4 largest metropolitan areas of Texas: Houston, Dallas/Ft. Worth, San Antonio, and Austin. At Wave 8 (June, 2018), retention remained high, at 85%; the oldest cohort is now 1 year post high school. We propose to follow these cohorts for an additional 6 waves of data collection, every 6 months, to track them all through high school (1, 3, and 5 years post-graduation), into young adulthood. Our web-based surveys include robust measures of ENDS use and other tobacco use behaviors; nicotine dependence; and a broad spectrum of potential risk factors, including intrapersonal, interpersonal, and environmental influences. Growth mixture models shall be applied to these data to empirically identify stable developmental patterns in ENDS use behaviors, from 11 to 22 years of age; we anticipate there will be substantial heterogeneity in them. We will be able to identify young adult outcomes of persistent patterns in ENDS use that begin in adolescence; and risk factors in adolescence that predict ENDS use trajectories that persist into young adulthood. The use of combustible tobacco products in adolescence and young adulthood will be considered, accordingly. Almost all (>95% of) existing cohorts and studies of ENDS use focus on either adolescents or young adults. Very few, like ours, are able to track adolescents into young adulthood to investigate developmental trajectories of risk.